[unreadable] With increasing success of modern cancer therapy in achieving long-term remission in many patients, second primary cancers are a rapidly increasing disease category. The increased occurrence of second primary tumors after a first primary tumor could arise from: (i) intensive medical surveillance after the first diagnosis; (ii) therapy induced exposure to chemical or physical carcinogens; and (iii) shared environmental and hereditary factors between the first and second cancer. Studies of multiple primary cancers can be rewarding for several reasons. First of all, they can help to identify common risk factors between a second and a first primary cancer, including environmental exposures and genetic factors. Studies on second primaries may also identify groups of cancer patients who are in need of increased surveillance aimed at early detection, allowing measures to prevent the occurrence of subsequent cancer incidence and mortality. Studies of second primary cancers, therefore, have the potential to provide relevant insights into cancer epidemiology, etiology and clinical practice. [unreadable] [unreadable] Until recently, most studies on second primary cancers have been based on individual cancer registries. This is problematic when trying to assess the consistency and validity of reported associations; specifically, when it comes to the more rare cancer types. In order to conduct a systematic analysis of second primary neoplasms for all cancer sites, we have developed an international multi-center study of second primary cancers incorporating 15 large cancer registries, which have been in operation for at least 25 years. Data pooling and verification is now complete for 13 of the 15 cancer registries, resulting in a cohort of 3,722,434 individuals with a cancer and 22,376,682 2-person years of follow-up. It is expected that the final database comprising information from all 15 cancer registries will be available by December 2002. Using this database we propose to conduct a systematic analysis of second primary cancers. This analysis will concentrate on specific hypotheses including: (i) an investigation of groups of cancers potentially related to specific exposures (e.g., ultraviolet light); (ii) an investigation of rare cancer types (e.g., bone cancer or sarcomas); and (iii) an investigation of second primary cancers which may be increased due to treatment of a first primary cancer (e.g., leukemia). [unreadable] [unreadable]